In the present study, we show that Neisseria gonorrhoeae lipooligosaccharide (LOS) can bind to the asialoglycoprotein receptor (ASGP-R) on human sperm. This work demonstrates the presence of ASGP-R on human sperm. Binding of purified ASGP-R ligand decreased in the presence of gonococci. Binding of purified iodinated gonococcal LOS identified a protein of molecular weight corresponding to that of human ASGP-R. The presence of excess unlabelled LOS blocked binding of iodinated gonococcal LOS. Binding of wild-type gonococcal LOS to sperm was higher than that of mutant LOS lacking the galactose ligand for ASGP-R. These data suggest that the ASGP-R on human sperm cells recognizes and binds wild-type gonococcal LOS. This interaction may contribute to the transmission of gonorrhea from infected males to their sexual partners.